Severe Combined Immune Deficiency (SCID) includes a spectrum of lethal genetic disorders resulting in profound deficiencies of T and B cell development and/or function, which render affected patients incapable of mounting protective immune responses against exogenous pathogens. Historically, children afflicted with SCID rarely survived the first year of life, succumbing to severe infections. The first cure of SCID was achieved in 1968 by transplantation of bone marrow (hematopoietic cell transplant - HCT) from an HLA compatible normal sibling, resulting in reconstitution of both T and B cell immunity. Since that time, more than 700 SCID patients in North America have been treated with HCT from matched siblings, haplo-identical parents, or unrelated adult donors or umbilical cord blood. While outcomes are generally good, not all patients survive and multiple patient-, donor- and transplant procedural differences may underlie the prognosis in each case. We have constructed a multi-institutional consortium to study this large cohort of patients, with the goal of identifying prognostic factors and defining optimal treatment approaches. In Specific Aim 1, we will perform a retrospective analysis of patients with the different forms of SCID who have received HCT at the participating institutions. We will analyze the impact that patient-, donor-, and transplantrelated factors have on long-term outcome. This study will also provide the first multicenter analysis of the effects of SCID genotype on the outcome of transplant. In Specific Aim 2, we will perform a cross-sectional analysis of long-term survivors after HCT for SCID, to characterize current level of T, B and NK cell chimerism and function, and clinical status in terms of health, growth and both physical and neurocognitive development. We will then analyze these results in relation to information gathered in the retrospective study to determine whether and to what degree SCID genotype, type of transplant applied or other clinical variables contribute to the patient's long-term outcome. These studies will produce important information on the outcomes of HCT for SCID and guide future clinical trials.